The invention relates to microfabricated devices for chemical and biological analysis, and more particularly to the integration of microfluidic and electronic components.
Microfluidic technology is utilized to create systems that can perform chemical and biological analysis on a much smaller scale than previous techniques. A popular use of microfluidic systems is in the analysis of DNA molecules. Microfluidic systems for analysis, chemical and biological processing, and sample preparation may include some combination of the following elements: pre- and post-processing fluidic handling components, microfluidic components, microfluidic-to-system interface components, electrical and electronics components, environmental control components, and data analysis components.
As microfluidic systems reduce in size and increase in complexity, there is a growing need for electronic and electrical processing support to enhance the analysis capabilities. Known microfluidic systems provide electronic and electrical processing support by performing operations such as voltage/current sourcing, signal sourcing, signal detection, signal processing, signal feedback, and data processing separately from the microfluidic system. In some instances separation of the electronic processing and microfluidic functions is desirable. For example, a relatively large power supply is required in order to apply a high voltage to a microfluidic channel for electrophoresis, and it is best to locate the power supply separate from the microfluidic system. As another example, data analysis is best performed using a computer that is separate from the microfluidic system.
However, some electrical processes have requirements that are difficult to meet utilizing electrical components that are separate from the microfluidic system. For example, very low energy signals which are detected from microfluidic systems tend to degrade as they are conducted away from the microfluidic system to a separate signal processing component. As a result of the tendency for signal degradation, it is preferable to amplify the detected signals before they degrade. On-system electrical processing is also desired in cases where information gathered from many sensors on a microfluidic system must be used to control processes on the microfluidic chip. For example, a temperature system input might be used to control heaters of a microfluidic system.
One technique for providing signal detection for a microfluidic system involves a single photodiode which is bonded onto a microfluidics chip as disclosed in the article entitled xe2x80x9cAn Optical MEMS-based Fluorescence Detection Scheme with Applications to Capillary Electrophoresis,xe2x80x9d by K. D. Kramer et al. (SPIE Conference on Microfluidic Devices and Systems, September 1998, SPIE Vol. 3515, pages 7-85.) Although a single photodiode is bonded onto the microfluidics chip, the photodiode is simply an electrical transducer and has no electronics signal processing or system control capability.
As described in the article entitled xe2x80x9cMicrofabricated Devices for Genetic Diagnostics,xe2x80x9d by Carlos H. Mastrangelo et al. (Proceedings of the IEEE, Vol. 86, No. 8, August 1998, pages 1769-1787), electronics have also been integrated directly onto the same substrate as a microfluidic system. Mastrangelo et al. have included the following devices on a silicon substrate: fluidic components, electrical driving components, diode detection components, and fluidic control elements (e.g., thermal valving). Although Mastrangelo et al. disclose integrated microfluidic and electronic components, the microfluidic and electronic components are fabricated on the same substrate. Fabricating both microfluidic and electronic components on the same substrate is not only more costly and difficult than fabricating microfluidic components, but also limits the selection of materials and processes available to fabricate the components. Further, the quality of the fabricated components is more easily controlled when the components are fabricated separately using known techniques.
Microfluidic systems have been fabricated in polymer, glass, silicon, and ceramic substrates. A microfluidic component fabricated on or in silicon can have electrical and data analysis components fabricated directly onto the silicon substrate as described by Mastrangelo, et al. However, this is not easily achieved on polymer or glass substrates. Polymer and glass substrates are the most useful substrates for microfluidic applications and therefore it is desirable to integrate polymer or glass substrates with electronics components. In view of the need to have electronics components in close proximity with microfluidic components and in view of the preference for polymer or glass microfluidic substrates, what is needed is a microfluidic system having a microfluidic component, ideally formed of polymer or glass, that is integrated with an electronics component.
A microfluidic component having a microfluidic channel is bonded to an electronics component having a circuit for processing signals related to the microfluidic component. In one embodiment, the electronics component is a prefabricated integrated circuit chip that includes signal processing and/or process control circuits that provide a substantially higher degree of functionality than a mere photodiode. The microfluidic component of the invention is preferably made of polymer and the integrated circuit chip is preferably bonded to the microfluidic component using a flip chip type process, common to the integrated circuit industry. The bonding of the microfluidic component to the electronics component provides a modular architecture in which different combinations of microfluidic components and electronics components can be used to create customized processing and analysis tools.
In a preferred embodiment, the microfluidic component includes a substrate that has features such as microfluidic channels, microfluidic compartments, and microfluidic flow control elements. Therefore, the microfluidic component may include known features such as capillary channels, separation channels, detection channels, valves and pumps.
The microfluidic component may be fabricated by direct means such as photolithographic processes, wet or dry chemical etching, laser ablation, or traditional machining. The microfluidic component may also be fabricated by indirect means such as injection molding, hot embossing, casting, or other processes that utilize a mold or patterned tool to form the features of the microfluidic component. The microfluidic substrate is made of a material such as polymer, glass, silicon, metal, or ceramic. A polymer such as polyimide or polymethylmethacrylate (PMMA) is preferred. The microfluidic component is substantially fabricated before the electronic component is bonded to it.
In addition to the microfluidic features, the microfluidic component may include conductive traces that are formed within the substrate and/or on the surface of the substrate. The conductive traces provide electrical connection between the electronics component and various electrical features on or in the microfluidic component. These electrical features may include: (1) direct contacts to the fluid; (2) elements which, either in contact with or not in contact with the fluid, control the flow or the operation of the fluid or its contents; (3) sensors in direct contact with the fluid; (4) sensors that do not directly contact the fluid; (5) electrical heating or cooling elements integrated in or on the microfluidic component; (6) elements that can affect surface change within the microfluidic component; and (7) active microfluidic control elements such as valves, pumps, and mixers. Conductive traces may also lead to contact pads on the microfluidic component that provide electrical connections to off-component systems such as signal processors, signal readout devices, power supplies, and/or data storage systems. Providing contact pads on the microfluidic component for connection to off-component systems may eliminate the need to provide such contact pads on the electronics component.
While the electronics component may be composed of discrete electrical elements on a common substrate, such as a conventional printed circuit board, the component is preferably a prefabricated integrated circuit that may perform any of a variety of functions. The prefabricated integrated circuit may include a combination of op-amps, transistors, diodes, multiplexers, switches, filters, etc., that perform functions such as signal detection, signal processing, buffering, and/or control functions. The electronics component can be, for example, an application specific integrated circuit (ASIC). The electronics component is preferably connected to the microfluidic component using a flip-chip connection such as solder-bump attachment, gold-plating attachment, or electrically conductive adhesive attachment. Preferably, this component is an electrical component that is mounted within the area of the microfluidic component, such that there is no overhang by the electrical component over the side of the microfluidic component. However, a cantilevered electronics component may be used as a means of exposing contact pads for direct connection of the electronics component to an off-component system. As an alternative to the integrated circuit chip, the electronics component consists of discrete electrical devices mounted on a suitable substrate, such as a printed circuit board, which is then bonded to the microfluidic component using one of the above methods.
Similar to the microfluidic component, the electronics component is fabricated in a separate operation utilizing either conventional semiconductor processing techniques or assembly of discrete electrical elements such as resistors, capacitors, operational amplifiers, and the like. The electronics component may include a combination of memory, signal detection, signal processing, and control circuitry. The signal detection circuitry may detect electrical fields, magnetic fields, conductivity, resistivity, electrical current, dielectric constants, chemical properties, temperature, pressure, and/or light, depending on the operational requirements of the microfluidic component. The signal processing circuitry may, for example, amplify a signal, filter a signal, convert a signal from analog to digital, and/or make logical decisions based upon signal inputs. The control circuitry may provide voltage control, current control, temperature control, and/or clock signal generation.
Because the microfluidics component and the electronics component are separate devices, the electronics component can be bonded to the microfluidic component in various locations. For example, the electronics component can be bonded to the microfluidics component such that it is not directly over any microfluidic channels or chambers. Alternatively, the electronics component can be bonded to the microfluidics component such that it is directly over a microfluidic channel or chamber so as to provide direct signal detection by the electronics component over the channel, chamber, or other feature. As another possibility, the system may include more than one electronic component bonded on the same side or on opposite sides of the microfluidic component.
In one embodiment of the invention, the electronics component functions to provide an on-system feedback loop between the microfluidic component and the electronics component. For example, the electronics component can signal a heater to monitor the temperature at a particular area of the microfluidic component. In response to the monitored temperature, the electronics component can adjust the temperature on the microfluidics component as needed to achieve or maintain a desired condition. Other on-system process controls can be implemented between the microfluidic component and the electronics component to provide functionality and/or enhanced performance.
Since the electronics component and the microfluidic component are separate devices that are bonded to each other, the components can be manufactured separately utilizing quality control procedures that are specific to each type of component. In addition, because the electronics component and the microfluidic component are separate devices, the components can be interchanged with other microfluidic and electronics components to create customized processing and analysis tools. For example, different integrated circuits can be utilized with a single design of microfluidics component to create new systems.